Genetic Dissection of Epidermal Growth Factor Receptor Signaling during Luteinizing Hormone-Induced Oocyte Maturation

Recent evidence that luteinizing hormone (LH) stimulation of ovulatory follicles causes transactivation of the epidermal growth factor receptor (EGFR) has provided insights into the mechanisms of ovulation. However, the complete array of signals that promote oocyte reentry into the meiotic cell cycle in the follicle are still incompletely understood. To elucidate the signaling downstream of EGFR involved in oocyte maturation, we have investigated the LH responses in granulosa cells with targeted ablation of EGFR. Oocyte maturation and ovulation is disrupted when EGFR expression is progressively reduced. In granulosa cells from mice with either global or granulosa cell-specific disruption of EGFR signaling, LH-induced phosphorylation of MAPK3/1, p38MAPK, and connexin-43 is impaired. Although the LH-induced decrease in cGMP is EGFR-dependent in wild type follicles, LH still induces a decrease in cGMP in Egfrdelta/f Cyp19-Cre follicles. Thus compensatory mechanisms appear activated in the mutant. Spatial propagation of the LH signal in the follicle also is dependent on the EGF network, and likely is important for the control of signaling to the oocyte. Thus, multiple signals and redundant pathways contribute to regulating oocyte reentry into the cell cycle

Dietary phytochemicals, HDAC inhibition, and DNA damage/repair defects in cancer cells

Genomic instability is a common feature of cancer etiology. This provides an avenue for therapeutic intervention, since cancer cells are more susceptible than normal cells to DNA damaging agents. However, there is growing evidence that the epigenetic mechanisms that impact DNA methylation and histone status also contribute to genomic instability. The DNA damage response, for example, is modulated by the acetylation status of histone and non-histone proteins, and by the opposing activities of histone acetyltransferase and histone deacetylase (HDAC) enzymes. Many HDACs overexpressed in cancer cells have been implicated in protecting such cells from genotoxic insults. Thus, HDAC inhibitors, in addition to unsilencing tumor suppressor genes, also can silence DNA repair pathways, inactivate non-histone proteins that are required for DNA stability, and induce reactive oxygen species and DNA double-strand breaks. This review summarizes how dietary phytochemicals that affect the epigenome also can trigger DNA damage and repair mechanisms. Where such data is available, examples are cited from studies in vitro and in vivo of polyphenols, organosulfur/organoselenium compounds, indoles, sesquiterpene lactones, and miscellaneous agents such as anacardic acid. Finally, by virtue of their genetic and epigenetic mechanisms, cancer chemopreventive agents are being redefined as chemo- or radio-sensitizers. A sustained DNA damage response coupled with insufficient repair may be a pivotal mechanism for apoptosis induction in cancer cells exposed to dietary phytochemicals. Future research, including appropriate clinical investigation, should clarify these emerging concepts in the context of both genetic and epigenetic mechanisms dysregulated in cancer, and the pros and cons of specific dietary intervention strategies

Amniotic fluid embolism: A rare complication of second-trimester amniocentesis

Amniotic fluid embolism occurring following diagnostic amniocentesis is extremely rare. Only 2 cases have been reported in the English literature over the past 55 years, the most recent one approximately 3 decades ago. We present a case of amniocentesis at 24 weeks' gestation that was performed as part of an evaluation of abnormal fetal ultrasound findings. Immediately following amniotic fluid aspiration, maternal hemodynamic collapse occurred, initially diagnosed and treated as anaphylactic shock. Shortly after initial therapy, coagulopathy was noted and amniotic fluid syndrome suspected. Rapid response restored maternal hemodynamic stability; however, the fetus had suffered fatal damage

Amniotic fluid embolism: A rare complication of second-trimester amniocentesis

Amniotic fluid embolism occurring following diagnostic amniocentesis is extremely rare. Only 2 cases have been reported in the English literature over the past 55 years, the most recent one approximately 3 decades ago. We present a case of amniocentesis at 24 weeks' gestation that was performed as part of an evaluation of abnormal fetal ultrasound findings. Immediately following amniotic fluid aspiration, maternal hemodynamic collapse occurred, initially diagnosed and treated as anaphylactic shock. Shortly after initial therapy, coagulopathy was noted and amniotic fluid syndrome suspected. Rapid response restored maternal hemodynamic stability; however, the fetus had suffered fatal damage

New Israeli sonographic estimated fetal weight growth curves as compared to current birth weight growth curves: On what should diagnosis of intrauterine growth disorders be based?

Background Two types of growth curves are commonly used to diagnose fetal growth disorders: neonatal birth weight (BW) and sonographic estimated fetal weight (EFW). The debate as to which growth curve to use is universal. Objectives To establish sonographic EFW growth curves for the Israeli population and to assess whether the use of the BW growth curves currently adapted in Israel leads to underdiagnosis of intrauterine growth disorders. Methods Biometric data collected during a 6 year period was analyzed to establish sonographic EFW growth curves between 15–42 weeks of gestation for the Israeli population. Growth curves were compared to previously published sonographic EFW growth curves. A comparison with the Israeli BW growth curves was performed to assess the possibility of underdiagnosis of intrauterine growth disorders. Results Out of 42,778 sonographic EFW studies, 31,559 met the inclusion criteria. The sonographic EFW growth curves from the current study resembled the EFW curves previously published. The comparison of the current sonographic EFW and BW growth curves revealed under-diagnosis of intrauterine growth disorders during the preterm period. Four percent of the fetuses assessed between 26–34 weeks would have been suspected of being growth restricted; 2.8 percent of the fetuses assessed between 30–36 weeks would have been suspected of having macrosomia, based on the BW growth curves. Conclusions New Israeli sonographic EFW growth curves resemble previously published sonographic EFW curves. Using BW growth curves may lead to the under-diagnosis of growth disorders. We recommend adopting sonographic EFW growth to diagnose intrauterine growth disorders.</p

Sliding sign for intra-abdominal adhesion prediction before repeat cesarean delivery

Background The sliding sign (the relative motion between the abdominal and uterine wall as assessed by ultrasonography) may help identify severe intraabdominal adhesions before repeat cesarean delivery. Methods We conducted a prospective observational study of scheduled repeat cesarean deliveries. Using transabdominal ultrasonography, while the parturient breathed deeply, the ultrasonographer recorded a video clip in a sagittal plane lateral to the umbilicus. These clips were assessed for the presence (sliding-positive) or absence (sliding-negative) of relative movement between the maternal abdominal and uterine wall. Surgeons blinded to ultrasonography results graded the severity of intraperitoneal adhesions intraoperatively. Study outcomes were the accuracy of the preoperative sliding sign for prediction of severe adhesions and its association with surgical times and bleeding. Experience We recruited 370 women. A negative sliding sign was associated with severe adhesions (sensitivity 56%, 95% CI 35–76; specificity 95%, 95% CI 93– 97). A similar accuracy (sensitivity 64%, 95% CI 43–82; specificity 94%, 95% CI 92–97) was achieved by combining the sliding sign with a history of adhesions in the previous surgery. In multivariable models, a negative sliding sign was significantly correlated with a longer interval from skin incision to delivery and increased risk for bleeding. Conclusion A negative sliding sign predicts severe intra-abdominal adhesions encountered during repeat cesarean delivery, longer time to delivery, and a higher chance of bleeding.</p

New Israeli sonographic estimated fetal weight growth curves as compared to current birth weight growth curves: On what should diagnosis of intrauterine growth disorders be based?

Background Two types of growth curves are commonly used to diagnose fetal growth disorders: neonatal birth weight (BW) and sonographic estimated fetal weight (EFW). The debate as to which growth curve to use is universal. Objectives To establish sonographic EFW growth curves for the Israeli population and to assess whether the use of the BW growth curves currently adapted in Israel leads to underdiagnosis of intrauterine growth disorders. Methods Biometric data collected during a 6 year period was analyzed to establish sonographic EFW growth curves between 15–42 weeks of gestation for the Israeli population. Growth curves were compared to previously published sonographic EFW growth curves. A comparison with the Israeli BW growth curves was performed to assess the possibility of underdiagnosis of intrauterine growth disorders. Results Out of 42,778 sonographic EFW studies, 31,559 met the inclusion criteria. The sonographic EFW growth curves from the current study resembled the EFW curves previously published. The comparison of the current sonographic EFW and BW growth curves revealed under-diagnosis of intrauterine growth disorders during the preterm period. Four percent of the fetuses assessed between 26–34 weeks would have been suspected of being growth restricted; 2.8 percent of the fetuses assessed between 30–36 weeks would have been suspected of having macrosomia, based on the BW growth curves. Conclusions New Israeli sonographic EFW growth curves resemble previously published sonographic EFW curves. Using BW growth curves may lead to the under-diagnosis of growth disorders. We recommend adopting sonographic EFW growth to diagnose intrauterine growth disorders.</p

Sliding sign for intra-abdominal adhesion prediction before repeat cesarean delivery

Background The sliding sign (the relative motion between the abdominal and uterine wall as assessed by ultrasonography) may help identify severe intraabdominal adhesions before repeat cesarean delivery. Methods We conducted a prospective observational study of scheduled repeat cesarean deliveries. Using transabdominal ultrasonography, while the parturient breathed deeply, the ultrasonographer recorded a video clip in a sagittal plane lateral to the umbilicus. These clips were assessed for the presence (sliding-positive) or absence (sliding-negative) of relative movement between the maternal abdominal and uterine wall. Surgeons blinded to ultrasonography results graded the severity of intraperitoneal adhesions intraoperatively. Study outcomes were the accuracy of the preoperative sliding sign for prediction of severe adhesions and its association with surgical times and bleeding. Experience We recruited 370 women. A negative sliding sign was associated with severe adhesions (sensitivity 56%, 95% CI 35–76; specificity 95%, 95% CI 93– 97). A similar accuracy (sensitivity 64%, 95% CI 43–82; specificity 94%, 95% CI 92–97) was achieved by combining the sliding sign with a history of adhesions in the previous surgery. In multivariable models, a negative sliding sign was significantly correlated with a longer interval from skin incision to delivery and increased risk for bleeding. Conclusion A negative sliding sign predicts severe intra-abdominal adhesions encountered during repeat cesarean delivery, longer time to delivery, and a higher chance of bleeding.</p